Kerri Wachter

WASHINGTON — When administering perioperative steroids to patients with suspected tertiary adrenal insufficiency, it's best to use the smallest possible dose for the shortest possible period of time.

“We should do our best to match the stress of the surgical procedure with the dose,” said Dr. Darrell W. Harrington, chief of the division of general internal medicine at Harbor-University of California, Los Angeles Medical Center.

The potential for adrenal crises poses a challenge in patients who are subjected to surgical stress but who are not receiving adequate corticosteroid supplementation. Data are inadequate “to allow reliable prediction of which patients are at risk for tertiary adrenal insufficiency,” he said at the annual meeting of the American College of Physicians.

“What we think we know is that there is no significant suppression if patients take a low dose [of steroids] daily.” Alternately, if patients take an every-other-day dose—usually less than 10 mg prednisone equivalent—there is little hypothalamic-pituitary-adrenal (HPA) axis suppression. Abbreviated exposures, ranging from 5 days to 3 weeks, are probably not associated with significant HPA axis suppression.

However, significant suppression does occur with high doses, superpotent topical steroids, and inhaled corticosteroids. Recovery after prolonged exposure may take as little as 5 days, or as long as a year.

“Unfortunately, there are a lot of patients who fall in between,” Dr. Harrington said. The data for these patients are inconsistent. Most patients on chronic steroids or with a history of steroid use do not have an obvious diagnosis of tertiary adrenal insufficiency. “We have to rely on clinical intuition to make this diagnosis.”

A random cortisol measurement works well at identifying patients who are likely to have HPA reserve. In addition, an adrenocorticotropic hormone (ACTH) stimulation test resulting in an incremental increase of cortisol greater than 9 mcg/dL indicates adequate HPA reserve. But biochemical abnormalities revealed by such tests “do not correlate or predict safety from a clinical events point of view,” Dr. Harrington noted.

The potential for impaired wound healing and increased infection rates related to the perioperative use of exogenous steroids makes some clinicians reluctant to adequately supplement. No clear, consistent evidence shows that wound healing is substantially delayed or impaired when patients are given short courses of perioperative steroids. And data from case series suggest that limited exposure to steroids in surgery patients is associated with a very limited increase in infection risk.

Dr. Harrington reported that he had significant financial relationships with Sanofi-Aventis, Eisai Inc., GlaxoSmithKline, and Pfizer Inc.

WASHINGTON — When administering perioperative steroids to patients with suspected tertiary adrenal insufficiency, it's best to use the smallest possible dose for the shortest possible period of time.

“We should do our best to match the stress of the surgical procedure with the dose,” said Dr. Darrell W. Harrington, chief of the division of general internal medicine at Harbor-University of California, Los Angeles Medical Center.

The potential for adrenal crises poses a challenge in patients who are subjected to surgical stress but who are not receiving adequate corticosteroid supplementation. Data are inadequate “to allow reliable prediction of which patients are at risk for tertiary adrenal insufficiency,” he said at the annual meeting of the American College of Physicians.

“What we think we know is that there is no significant suppression if patients take a low dose [of steroids] daily.” Alternately, if patients take an every-other-day dose—usually less than 10 mg prednisone equivalent—there is little hypothalamic-pituitary-adrenal (HPA) axis suppression. Abbreviated exposures, ranging from 5 days to 3 weeks, are probably not associated with significant HPA axis suppression.

However, significant suppression does occur with high doses, superpotent topical steroids, and inhaled corticosteroids. Recovery after prolonged exposure may take as little as 5 days, or as long as a year.

“Unfortunately, there are a lot of patients who fall in between,” Dr. Harrington said. The data for these patients are inconsistent. Most patients on chronic steroids or with a history of steroid use do not have an obvious diagnosis of tertiary adrenal insufficiency. “We have to rely on clinical intuition to make this diagnosis.”

A random cortisol measurement works well at identifying patients who are likely to have HPA reserve. In addition, an adrenocorticotropic hormone (ACTH) stimulation test resulting in an incremental increase of cortisol greater than 9 mcg/dL indicates adequate HPA reserve. But biochemical abnormalities revealed by such tests “do not correlate or predict safety from a clinical events point of view,” Dr. Harrington noted.

The potential for impaired wound healing and increased infection rates related to the perioperative use of exogenous steroids makes some clinicians reluctant to adequately supplement. No clear, consistent evidence shows that wound healing is substantially delayed or impaired when patients are given short courses of perioperative steroids. And data from case series suggest that limited exposure to steroids in surgery patients is associated with a very limited increase in infection risk.

Dr. Harrington reported that he had significant financial relationships with Sanofi-Aventis, Eisai Inc., GlaxoSmithKline, and Pfizer Inc.

WASHINGTON — When administering perioperative steroids to patients with suspected tertiary adrenal insufficiency, it's best to use the smallest possible dose for the shortest possible period of time.

“We should do our best to match the stress of the surgical procedure with the dose,” said Dr. Darrell W. Harrington, chief of the division of general internal medicine at Harbor-University of California, Los Angeles Medical Center.

The potential for adrenal crises poses a challenge in patients who are subjected to surgical stress but who are not receiving adequate corticosteroid supplementation. Data are inadequate “to allow reliable prediction of which patients are at risk for tertiary adrenal insufficiency,” he said at the annual meeting of the American College of Physicians.

“What we think we know is that there is no significant suppression if patients take a low dose [of steroids] daily.” Alternately, if patients take an every-other-day dose—usually less than 10 mg prednisone equivalent—there is little hypothalamic-pituitary-adrenal (HPA) axis suppression. Abbreviated exposures, ranging from 5 days to 3 weeks, are probably not associated with significant HPA axis suppression.

However, significant suppression does occur with high doses, superpotent topical steroids, and inhaled corticosteroids. Recovery after prolonged exposure may take as little as 5 days, or as long as a year.

“Unfortunately, there are a lot of patients who fall in between,” Dr. Harrington said. The data for these patients are inconsistent. Most patients on chronic steroids or with a history of steroid use do not have an obvious diagnosis of tertiary adrenal insufficiency. “We have to rely on clinical intuition to make this diagnosis.”

A random cortisol measurement works well at identifying patients who are likely to have HPA reserve. In addition, an adrenocorticotropic hormone (ACTH) stimulation test resulting in an incremental increase of cortisol greater than 9 mcg/dL indicates adequate HPA reserve. But biochemical abnormalities revealed by such tests “do not correlate or predict safety from a clinical events point of view,” Dr. Harrington noted.

The potential for impaired wound healing and increased infection rates related to the perioperative use of exogenous steroids makes some clinicians reluctant to adequately supplement. No clear, consistent evidence shows that wound healing is substantially delayed or impaired when patients are given short courses of perioperative steroids. And data from case series suggest that limited exposure to steroids in surgery patients is associated with a very limited increase in infection risk.

Dr. Harrington reported that he had significant financial relationships with Sanofi-Aventis, Eisai Inc., GlaxoSmithKline, and Pfizer Inc.

A new imaging system recently cleared for marketing by the Food and Drug Administration offers cardiologists help in assessing coronary artery plaque content to determine if the deposit is vulnerable to rupture.

Plaques containing large lipid cores have been associated with plaque rupture and thrombosis in patients with coronary artery disease. The ability to assess the makeup of coronary artery plaques and identify those patients at greatest risk of plaque rupture and subsequent heart attack has become something of a holy grail for cardiology.

The LipiScan near-infrared catheter imaging system (InfraReDx Inc.) “is the first device that can help assess the chemical makeup of coronary artery plaques and help physicians identify those plaques with lipid cores, which may be of particular concern,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in a press release.

The InfraReDx system relies on near-infrared spectroscopy (NIRS), which utilizes the near-infrared region of the electromagnetic spectrum (roughly 800–2,500 nm) to determine the chemical makeup of a plaque. One advantage is that NIR radiation can typically penetrate much further into a sample than even mid-infrared waves, making the technique useful in probing bulk material with little or no sample preparation.

The technique involves targeting a material with electromagnetic radiation over the NIR range. The amount of energy absorbed by material at different wavelengths results in a spectrum that serves as a unique fingerprint for a specific compound. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well defined.

The device is cleared for use by physicians who are evaluating patients with symptoms of coronary heart disease during coronary angiography.

“It's an excellent technology to identify lipid-rich plaques and vulnerable plaques in the coronary arterial wall,” said Dr. George Beller, professor of internal medicine and interim chief of the division of cardiovascular medicine at the University of Virginia, Charlottesville. “Unlike other types of devices, near-infrared light can penetrate through blood to get signals from structures that are actually several millimeters deep relative to the tissue surface.”

The technology has the potential to alter patient management. For example, a patient catheterized following acute coronary syndrome who is found to have lipid-laden plaques with thin fibrous caps might be more likely to get more aggressive medical management after stenting of the main lesion.

“The next question is whether it will prove to be a clinically useful tool,” Dr. Beller said.

The Spectroscopic Assessment of Coronary Lipid (SPECTACL) study, aimed at demonstrating that spectra obtained in the coronaries of 125 patients with stable and unstable coronary artery disease are similar to postmortem specimens, is still ongoing. The trial's secondary end point is to determine the presence of lipid-rich plaques in the coronary arteries of these patients.

Although NIRS shows promise, research continues on the use of other imaging modalities to identify vulnerable plaques.

“The [NIRS] technique may have advantages over intravascular ultrasound [IVUS] or virtual histology IVUS, but that remains to be seen because that technique is also being evaluated to distinguish between predominantly fibrous plaques and those which have predominantly necrotic cores that are lipid laden,” Dr. Beller said.

The search also goes on for noninvasive means of evaluating plaque vulnerability. “This technology doesn't preclude the major goal of identifying plaques noninvasively, with nuclear or MR or CT techniques. That is still a very high priority,” he said.

A new imaging system recently cleared for marketing by the Food and Drug Administration offers cardiologists help in assessing coronary artery plaque content to determine if the deposit is vulnerable to rupture.

Plaques containing large lipid cores have been associated with plaque rupture and thrombosis in patients with coronary artery disease. The ability to assess the makeup of coronary artery plaques and identify those patients at greatest risk of plaque rupture and subsequent heart attack has become something of a holy grail for cardiology.

The LipiScan near-infrared catheter imaging system (InfraReDx Inc.) “is the first device that can help assess the chemical makeup of coronary artery plaques and help physicians identify those plaques with lipid cores, which may be of particular concern,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in a press release.

The InfraReDx system relies on near-infrared spectroscopy (NIRS), which utilizes the near-infrared region of the electromagnetic spectrum (roughly 800–2,500 nm) to determine the chemical makeup of a plaque. One advantage is that NIR radiation can typically penetrate much further into a sample than even mid-infrared waves, making the technique useful in probing bulk material with little or no sample preparation.

The technique involves targeting a material with electromagnetic radiation over the NIR range. The amount of energy absorbed by material at different wavelengths results in a spectrum that serves as a unique fingerprint for a specific compound. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well defined.

The device is cleared for use by physicians who are evaluating patients with symptoms of coronary heart disease during coronary angiography.

“It's an excellent technology to identify lipid-rich plaques and vulnerable plaques in the coronary arterial wall,” said Dr. George Beller, professor of internal medicine and interim chief of the division of cardiovascular medicine at the University of Virginia, Charlottesville. “Unlike other types of devices, near-infrared light can penetrate through blood to get signals from structures that are actually several millimeters deep relative to the tissue surface.”

The technology has the potential to alter patient management. For example, a patient catheterized following acute coronary syndrome who is found to have lipid-laden plaques with thin fibrous caps might be more likely to get more aggressive medical management after stenting of the main lesion.

“The next question is whether it will prove to be a clinically useful tool,” Dr. Beller said.

The Spectroscopic Assessment of Coronary Lipid (SPECTACL) study, aimed at demonstrating that spectra obtained in the coronaries of 125 patients with stable and unstable coronary artery disease are similar to postmortem specimens, is still ongoing. The trial's secondary end point is to determine the presence of lipid-rich plaques in the coronary arteries of these patients.

Although NIRS shows promise, research continues on the use of other imaging modalities to identify vulnerable plaques.

“The [NIRS] technique may have advantages over intravascular ultrasound [IVUS] or virtual histology IVUS, but that remains to be seen because that technique is also being evaluated to distinguish between predominantly fibrous plaques and those which have predominantly necrotic cores that are lipid laden,” Dr. Beller said.

The search also goes on for noninvasive means of evaluating plaque vulnerability. “This technology doesn't preclude the major goal of identifying plaques noninvasively, with nuclear or MR or CT techniques. That is still a very high priority,” he said.

A new imaging system recently cleared for marketing by the Food and Drug Administration offers cardiologists help in assessing coronary artery plaque content to determine if the deposit is vulnerable to rupture.

Plaques containing large lipid cores have been associated with plaque rupture and thrombosis in patients with coronary artery disease. The ability to assess the makeup of coronary artery plaques and identify those patients at greatest risk of plaque rupture and subsequent heart attack has become something of a holy grail for cardiology.

The LipiScan near-infrared catheter imaging system (InfraReDx Inc.) “is the first device that can help assess the chemical makeup of coronary artery plaques and help physicians identify those plaques with lipid cores, which may be of particular concern,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in a press release.

The InfraReDx system relies on near-infrared spectroscopy (NIRS), which utilizes the near-infrared region of the electromagnetic spectrum (roughly 800–2,500 nm) to determine the chemical makeup of a plaque. One advantage is that NIR radiation can typically penetrate much further into a sample than even mid-infrared waves, making the technique useful in probing bulk material with little or no sample preparation.

The technique involves targeting a material with electromagnetic radiation over the NIR range. The amount of energy absorbed by material at different wavelengths results in a spectrum that serves as a unique fingerprint for a specific compound. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well defined.

The device is cleared for use by physicians who are evaluating patients with symptoms of coronary heart disease during coronary angiography.

“It's an excellent technology to identify lipid-rich plaques and vulnerable plaques in the coronary arterial wall,” said Dr. George Beller, professor of internal medicine and interim chief of the division of cardiovascular medicine at the University of Virginia, Charlottesville. “Unlike other types of devices, near-infrared light can penetrate through blood to get signals from structures that are actually several millimeters deep relative to the tissue surface.”

The technology has the potential to alter patient management. For example, a patient catheterized following acute coronary syndrome who is found to have lipid-laden plaques with thin fibrous caps might be more likely to get more aggressive medical management after stenting of the main lesion.

“The next question is whether it will prove to be a clinically useful tool,” Dr. Beller said.

The Spectroscopic Assessment of Coronary Lipid (SPECTACL) study, aimed at demonstrating that spectra obtained in the coronaries of 125 patients with stable and unstable coronary artery disease are similar to postmortem specimens, is still ongoing. The trial's secondary end point is to determine the presence of lipid-rich plaques in the coronary arteries of these patients.

Although NIRS shows promise, research continues on the use of other imaging modalities to identify vulnerable plaques.

“The [NIRS] technique may have advantages over intravascular ultrasound [IVUS] or virtual histology IVUS, but that remains to be seen because that technique is also being evaluated to distinguish between predominantly fibrous plaques and those which have predominantly necrotic cores that are lipid laden,” Dr. Beller said.

The search also goes on for noninvasive means of evaluating plaque vulnerability. “This technology doesn't preclude the major goal of identifying plaques noninvasively, with nuclear or MR or CT techniques. That is still a very high priority,” he said.

CHICAGO — The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. “With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy.

Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemo brain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to “get around” to doing things they know they should do.

Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships.

CHICAGO — The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. “With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy.

Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemo brain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to “get around” to doing things they know they should do.

Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships.

CHICAGO — The wakefulness-promoting drug modafinil (Provigil) reduced self-reported severe fatigue, according to a study of more than 600 cancer patients undergoing chemotherapy that was presented at the annual meeting of the American Society of Clinical Oncology.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle. They rated fatigue on a 10-point scale: mild (1-4), moderate (5-6), and severe (7-10). A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant. This was not surprising, Dr. Morrow said during a press briefing. “With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy.

Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemo brain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemo brain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemo brain. Cancer-related fatigue appears to particularly affect tasks associated with executive function. Cancer patients complain of not being able to “get around” to doing things they know they should do.

Cephalon Inc. provided modafinil and placebo for the trial. Dr. Morrow reported that he has no relevant financial relationships.

SAVANNAH, GA. — Women who have received lacerations requiring sutures as a result of childbirth might have poorer sexual function post partum than women who did not, according to data from questionnaires completed by 326 postpartum women.

Dr. Rebecca Rogers of the University of New Mexico, Albuquerque, presented study results in a poster session at the annual meeting of the Society of Gynecologic Surgeons. She and her colleagues followed 576 low-risk pregnant women who were cared for by midwives between 2005 and 2007. The women's cases were classified as minor or major trauma. Minor trauma was defined as no trauma or first-degree perineal, labial, periurethral, or clitoral lacerations. Major trauma was defined as second-, third-, or fourth-degree lacerations or any trauma requiring suturing. Women who had an episiotomy or who required operative delivery were excluded.

At follow-up, the women were asked if they had been sexually active since the birth. The 326 women who answered yes were asked to complete the Intimate Relationship Scale, a 12-item questionnaire designed to measure postpartum sexual function.

Of these women, 273 reported being sexually active at 3 months post partum. The majority of the women sustained some type of trauma, with only 16% delivering intact. Of those with trauma, most had minor trauma (70%). Women in the two groups differed by parity, length of active pushing, and education. Intimate Relationship Scale scores were not significantly different between women with major and minor trauma—36 vs. 33. However, women requiring sutures had significantly lower scores (mean 31) than did women who did not (mean 35.5) after adjusting for parity, length of pushing, and education.

Dr. Rogers disclosed that she is a speaker and investigator for Pfizer Inc. The meeting was jointly sponsored by the American College of Surgeons.

SAVANNAH, GA. — Women who have received lacerations requiring sutures as a result of childbirth might have poorer sexual function post partum than women who did not, according to data from questionnaires completed by 326 postpartum women.

Dr. Rebecca Rogers of the University of New Mexico, Albuquerque, presented study results in a poster session at the annual meeting of the Society of Gynecologic Surgeons. She and her colleagues followed 576 low-risk pregnant women who were cared for by midwives between 2005 and 2007. The women's cases were classified as minor or major trauma. Minor trauma was defined as no trauma or first-degree perineal, labial, periurethral, or clitoral lacerations. Major trauma was defined as second-, third-, or fourth-degree lacerations or any trauma requiring suturing. Women who had an episiotomy or who required operative delivery were excluded.

At follow-up, the women were asked if they had been sexually active since the birth. The 326 women who answered yes were asked to complete the Intimate Relationship Scale, a 12-item questionnaire designed to measure postpartum sexual function.

Of these women, 273 reported being sexually active at 3 months post partum. The majority of the women sustained some type of trauma, with only 16% delivering intact. Of those with trauma, most had minor trauma (70%). Women in the two groups differed by parity, length of active pushing, and education. Intimate Relationship Scale scores were not significantly different between women with major and minor trauma—36 vs. 33. However, women requiring sutures had significantly lower scores (mean 31) than did women who did not (mean 35.5) after adjusting for parity, length of pushing, and education.

Dr. Rogers disclosed that she is a speaker and investigator for Pfizer Inc. The meeting was jointly sponsored by the American College of Surgeons.

SAVANNAH, GA. — Women who have received lacerations requiring sutures as a result of childbirth might have poorer sexual function post partum than women who did not, according to data from questionnaires completed by 326 postpartum women.

Dr. Rebecca Rogers of the University of New Mexico, Albuquerque, presented study results in a poster session at the annual meeting of the Society of Gynecologic Surgeons. She and her colleagues followed 576 low-risk pregnant women who were cared for by midwives between 2005 and 2007. The women's cases were classified as minor or major trauma. Minor trauma was defined as no trauma or first-degree perineal, labial, periurethral, or clitoral lacerations. Major trauma was defined as second-, third-, or fourth-degree lacerations or any trauma requiring suturing. Women who had an episiotomy or who required operative delivery were excluded.

At follow-up, the women were asked if they had been sexually active since the birth. The 326 women who answered yes were asked to complete the Intimate Relationship Scale, a 12-item questionnaire designed to measure postpartum sexual function.

Of these women, 273 reported being sexually active at 3 months post partum. The majority of the women sustained some type of trauma, with only 16% delivering intact. Of those with trauma, most had minor trauma (70%). Women in the two groups differed by parity, length of active pushing, and education. Intimate Relationship Scale scores were not significantly different between women with major and minor trauma—36 vs. 33. However, women requiring sutures had significantly lower scores (mean 31) than did women who did not (mean 35.5) after adjusting for parity, length of pushing, and education.

Dr. Rogers disclosed that she is a speaker and investigator for Pfizer Inc. The meeting was jointly sponsored by the American College of Surgeons.

Poor cognitive function in childhood appears to be associated with the development of type 2 diabetes later in life, according to a study of more than 9,000 individuals.

“Poorer cognition function at age 11 years was associated with an increased risk of type 2 diabetes by age 42 years,” wrote Gunilla M. Olsson, Ph.D., of Uppsala University in Sweden and her colleagues (Diabetes Care 2008;31:514–6).

Type 2 diabetes previously has been associated with decreased cognitive function in adults, particularly older adults. The new findings suggest that “very early detection of subclinical disease and treatment may be of value in protecting against cognitive deficits,” the researchers noted.

The study involved individuals enrolled in the National Child Development Study, which is following all people born in the United Kingdom between March 3 and 9, 1958—approximately 17,000 births. Cognitive function was assessed at age 11 years using tests for general ability (verbal and nonverbal) and reading comprehension. Confirmed or possible diagnoses of type 2 diabetes at age 16 years were based on a medical examination and record review. Interviews at ages 33 and 42 years identified those with type 2 diabetes with a question about diabetes that does not require insulin injections. Pregnancy-related diabetes was excluded.

In all, 11,419 individuals were still participating at age 42 years. After excluding those with a confirmed or suspected diagnosis of diabetes (type 1 or 2) by age 16 years and those with type 1 diabetes or insufficient information on diabetes, 9,182 individuals were available for analysis.

Logistic regression analysis was used to estimate the risk of subsequent type 2 diabetes for each standard deviation change in test score. Models were adjusted for sex, birth weight, gestational age, parental social class, maternal smoking during pregnancy, age that mother left school, mother's age at delivery, presence of mild or severe mental retardation, disability, and ethnic origin. Separate models were adjusted for body mass index at age 7 years. Additional models were used to examine type 2 diabetes diagnosed after 33 years of age.

Cohort members with a diagnosis of type 2 diabetes after age 16 years had significantly lower assessment scores at age 11 years, even after adjustment for potential confounders. In all, 69 subjects were diagnosed with type 2 diabetes between the ages of 16 and 42 years. The average general ability score for those without a subsequent diagnosis of type 2 diabetes was 45 (out of a possible score of 79), compared with a score of 37 for those later diagnosed with type 2 diabetes. Likewise, the average reading comprehension score for those without a subsequent diagnosis of type 2 diabetes was 17 (out of a possible score of 35), compared with 13 for those later diagnosed with type 2 diabetes.

The odds ratios indicate a reduction in risk of later type 2 diabetes with one standard deviation increase in test scores—OR 0.67 for general ability scores and OR 0.58 for reading comprehension scores.

While exclusion of those with diabetes onset before age 33 years reduced the sample size with available data, lower test scores at age 11 years were still significantly associated with increased type 2 diabetes risk. This association of poorer childhood cognitive function with type 2 diabetes onset after age 33 years suggests that there might be a long delay between impaired cognition in childhood and symptomatic onset of type 2 diabetes, according to the study investigators.

“It is possible that cognitive deficits present in childhood influence lifestyle factors that increase the risk of type 2 diabetes. Alternately, poorer glycemic control or other shared risk factors may influence both cognitive development and the risk of type 2 diabetes,” the researchers wrote.

Poor cognitive function in childhood appears to be associated with the development of type 2 diabetes later in life, according to a study of more than 9,000 individuals.

“Poorer cognition function at age 11 years was associated with an increased risk of type 2 diabetes by age 42 years,” wrote Gunilla M. Olsson, Ph.D., of Uppsala University in Sweden and her colleagues (Diabetes Care 2008;31:514–6).

Type 2 diabetes previously has been associated with decreased cognitive function in adults, particularly older adults. The new findings suggest that “very early detection of subclinical disease and treatment may be of value in protecting against cognitive deficits,” the researchers noted.

The study involved individuals enrolled in the National Child Development Study, which is following all people born in the United Kingdom between March 3 and 9, 1958—approximately 17,000 births. Cognitive function was assessed at age 11 years using tests for general ability (verbal and nonverbal) and reading comprehension. Confirmed or possible diagnoses of type 2 diabetes at age 16 years were based on a medical examination and record review. Interviews at ages 33 and 42 years identified those with type 2 diabetes with a question about diabetes that does not require insulin injections. Pregnancy-related diabetes was excluded.

In all, 11,419 individuals were still participating at age 42 years. After excluding those with a confirmed or suspected diagnosis of diabetes (type 1 or 2) by age 16 years and those with type 1 diabetes or insufficient information on diabetes, 9,182 individuals were available for analysis.

Logistic regression analysis was used to estimate the risk of subsequent type 2 diabetes for each standard deviation change in test score. Models were adjusted for sex, birth weight, gestational age, parental social class, maternal smoking during pregnancy, age that mother left school, mother's age at delivery, presence of mild or severe mental retardation, disability, and ethnic origin. Separate models were adjusted for body mass index at age 7 years. Additional models were used to examine type 2 diabetes diagnosed after 33 years of age.

Cohort members with a diagnosis of type 2 diabetes after age 16 years had significantly lower assessment scores at age 11 years, even after adjustment for potential confounders. In all, 69 subjects were diagnosed with type 2 diabetes between the ages of 16 and 42 years. The average general ability score for those without a subsequent diagnosis of type 2 diabetes was 45 (out of a possible score of 79), compared with a score of 37 for those later diagnosed with type 2 diabetes. Likewise, the average reading comprehension score for those without a subsequent diagnosis of type 2 diabetes was 17 (out of a possible score of 35), compared with 13 for those later diagnosed with type 2 diabetes.

The odds ratios indicate a reduction in risk of later type 2 diabetes with one standard deviation increase in test scores—OR 0.67 for general ability scores and OR 0.58 for reading comprehension scores.

While exclusion of those with diabetes onset before age 33 years reduced the sample size with available data, lower test scores at age 11 years were still significantly associated with increased type 2 diabetes risk. This association of poorer childhood cognitive function with type 2 diabetes onset after age 33 years suggests that there might be a long delay between impaired cognition in childhood and symptomatic onset of type 2 diabetes, according to the study investigators.

“It is possible that cognitive deficits present in childhood influence lifestyle factors that increase the risk of type 2 diabetes. Alternately, poorer glycemic control or other shared risk factors may influence both cognitive development and the risk of type 2 diabetes,” the researchers wrote.

Poor cognitive function in childhood appears to be associated with the development of type 2 diabetes later in life, according to a study of more than 9,000 individuals.

“Poorer cognition function at age 11 years was associated with an increased risk of type 2 diabetes by age 42 years,” wrote Gunilla M. Olsson, Ph.D., of Uppsala University in Sweden and her colleagues (Diabetes Care 2008;31:514–6).

Type 2 diabetes previously has been associated with decreased cognitive function in adults, particularly older adults. The new findings suggest that “very early detection of subclinical disease and treatment may be of value in protecting against cognitive deficits,” the researchers noted.

The study involved individuals enrolled in the National Child Development Study, which is following all people born in the United Kingdom between March 3 and 9, 1958—approximately 17,000 births. Cognitive function was assessed at age 11 years using tests for general ability (verbal and nonverbal) and reading comprehension. Confirmed or possible diagnoses of type 2 diabetes at age 16 years were based on a medical examination and record review. Interviews at ages 33 and 42 years identified those with type 2 diabetes with a question about diabetes that does not require insulin injections. Pregnancy-related diabetes was excluded.

In all, 11,419 individuals were still participating at age 42 years. After excluding those with a confirmed or suspected diagnosis of diabetes (type 1 or 2) by age 16 years and those with type 1 diabetes or insufficient information on diabetes, 9,182 individuals were available for analysis.

Logistic regression analysis was used to estimate the risk of subsequent type 2 diabetes for each standard deviation change in test score. Models were adjusted for sex, birth weight, gestational age, parental social class, maternal smoking during pregnancy, age that mother left school, mother's age at delivery, presence of mild or severe mental retardation, disability, and ethnic origin. Separate models were adjusted for body mass index at age 7 years. Additional models were used to examine type 2 diabetes diagnosed after 33 years of age.

Cohort members with a diagnosis of type 2 diabetes after age 16 years had significantly lower assessment scores at age 11 years, even after adjustment for potential confounders. In all, 69 subjects were diagnosed with type 2 diabetes between the ages of 16 and 42 years. The average general ability score for those without a subsequent diagnosis of type 2 diabetes was 45 (out of a possible score of 79), compared with a score of 37 for those later diagnosed with type 2 diabetes. Likewise, the average reading comprehension score for those without a subsequent diagnosis of type 2 diabetes was 17 (out of a possible score of 35), compared with 13 for those later diagnosed with type 2 diabetes.

The odds ratios indicate a reduction in risk of later type 2 diabetes with one standard deviation increase in test scores—OR 0.67 for general ability scores and OR 0.58 for reading comprehension scores.

While exclusion of those with diabetes onset before age 33 years reduced the sample size with available data, lower test scores at age 11 years were still significantly associated with increased type 2 diabetes risk. This association of poorer childhood cognitive function with type 2 diabetes onset after age 33 years suggests that there might be a long delay between impaired cognition in childhood and symptomatic onset of type 2 diabetes, according to the study investigators.

“It is possible that cognitive deficits present in childhood influence lifestyle factors that increase the risk of type 2 diabetes. Alternately, poorer glycemic control or other shared risk factors may influence both cognitive development and the risk of type 2 diabetes,” the researchers wrote.

SAVANNAH, GA. — Fesoterodine appears to significantly improve the symptoms of overactive bladder in women with an apparent dose-related response, according to a subanalysis of pooled data from two phase III clinical trials involving more than 1,500 women.

Women randomized to either 4 mg or 8 mg of fesoterodine showed significantly greater improvement in the average number of micturitions per day, the average number of urgency urinary incontinence episodes per day, and perceived treatment response, Dr. Peter K. Sand reported in a poster presented at the annual meeting of the Society of Gynecologic Surgeons.

The study was funded by Schwarz BioSciences, a subsidiary of Schwarz Pharma AG, and Pfizer Inc. In 2006, Schwarz Pharma transferred rights for fesoterodine to Pfizer in exchange for an up-front payment of royalties on the combined sales of the drug, if approved. Dr. Sand disclosed that he is an adviser to and an investigator for Pfizer. In addition, another of the study authors is employed by Pfizer.

The researchers pooled data from two phase III randomized controlled trials, which involved male and female patients at least 18 years old with frequency and urgency urinary incontinence. Frequency was defined as at least eight micturitions in 24 hours; urgency urinary incontinence was defined as at least one episode in 24 hours. This subanalysis examined efficacy and tolerability in 1,543 women.

The women were randomized to 12 weeks of treatment with 4 mg fesoterodine (434), 8 mg fesoterodine (452), or placebo (430). One trial also included a positive control arm with 4 mg tolterodine extended release (227). Patients completed 3-day bladder diaries before randomization and at 2, 8, and 12 weeks after initiating treatment.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg fesoterodine in urgency urinary incontinence episodes per day, number of continent days per week, and perceived treatment response, Dr. Sand, a professor of obstetrics and gynecology at Northwestern University, Chicago, and his associates reported at the meeting, which was jointly sponsored by the American College of Surgeons.

The median change in number of micturitions per day from baseline to trial end (the primary end point) was significantly decreased for women on 4 mg fesoterodine (1.8), 8 mg fesoterodine (1.9), and 4 mg tolterodine (1.9), compared with placebo (1.0).

At 12 weeks, the mean decrease from baseline in the number of episodes of urgency urinary incontinence per day was 2.3 for women on 8 mg fesoterodine. Those on 4 mg fesoterodine, 4 mg tolterodine, and placebo had mean decreases from baseline of 1.9 episodes, 1.7 episodes, and 1.1 episodes per day, respectively. The difference was significantly greater for the treatment groups versus the placebo group.

Mean volume voided significantly increased from baseline in women on 4 mg fesoterodine (25.5 mL/void), 8 mg fesoterodine (32.1 mL/void), and 4 mg tolterodine (26.6 mL/void), compared with placebo (9.4 mL/void).

The researchers extrapolated the number of continent days per week from 3-day bladder diaries. The mean change from baseline was significantly increased for women taking 4 mg fesoterodine (2.5 days), 8 mg fesoterodine (3 days), and 4 mg tolterodine (2.3 days), compared with placebo (1.7 days). The change in continent days per week was significantly greater for women on 8 mg fesoterodine than for women on 4 mg tolterodine.

A positive treatment response was reported by 49%, 70%, 77%, and 74% in women receiving placebo, 4 mg fesoterodine, 8 mg fesoterodine, and 4 mg tolterodine, respectively. The most common treatment-emergent adverse events at the end of the study were dry mouth, constipation, urinary tract infection, and headache.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg.

SAVANNAH, GA. — Fesoterodine appears to significantly improve the symptoms of overactive bladder in women with an apparent dose-related response, according to a subanalysis of pooled data from two phase III clinical trials involving more than 1,500 women.

Women randomized to either 4 mg or 8 mg of fesoterodine showed significantly greater improvement in the average number of micturitions per day, the average number of urgency urinary incontinence episodes per day, and perceived treatment response, Dr. Peter K. Sand reported in a poster presented at the annual meeting of the Society of Gynecologic Surgeons.

The study was funded by Schwarz BioSciences, a subsidiary of Schwarz Pharma AG, and Pfizer Inc. In 2006, Schwarz Pharma transferred rights for fesoterodine to Pfizer in exchange for an up-front payment of royalties on the combined sales of the drug, if approved. Dr. Sand disclosed that he is an adviser to and an investigator for Pfizer. In addition, another of the study authors is employed by Pfizer.

The researchers pooled data from two phase III randomized controlled trials, which involved male and female patients at least 18 years old with frequency and urgency urinary incontinence. Frequency was defined as at least eight micturitions in 24 hours; urgency urinary incontinence was defined as at least one episode in 24 hours. This subanalysis examined efficacy and tolerability in 1,543 women.

The women were randomized to 12 weeks of treatment with 4 mg fesoterodine (434), 8 mg fesoterodine (452), or placebo (430). One trial also included a positive control arm with 4 mg tolterodine extended release (227). Patients completed 3-day bladder diaries before randomization and at 2, 8, and 12 weeks after initiating treatment.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg fesoterodine in urgency urinary incontinence episodes per day, number of continent days per week, and perceived treatment response, Dr. Sand, a professor of obstetrics and gynecology at Northwestern University, Chicago, and his associates reported at the meeting, which was jointly sponsored by the American College of Surgeons.

The median change in number of micturitions per day from baseline to trial end (the primary end point) was significantly decreased for women on 4 mg fesoterodine (1.8), 8 mg fesoterodine (1.9), and 4 mg tolterodine (1.9), compared with placebo (1.0).

At 12 weeks, the mean decrease from baseline in the number of episodes of urgency urinary incontinence per day was 2.3 for women on 8 mg fesoterodine. Those on 4 mg fesoterodine, 4 mg tolterodine, and placebo had mean decreases from baseline of 1.9 episodes, 1.7 episodes, and 1.1 episodes per day, respectively. The difference was significantly greater for the treatment groups versus the placebo group.

Mean volume voided significantly increased from baseline in women on 4 mg fesoterodine (25.5 mL/void), 8 mg fesoterodine (32.1 mL/void), and 4 mg tolterodine (26.6 mL/void), compared with placebo (9.4 mL/void).

The researchers extrapolated the number of continent days per week from 3-day bladder diaries. The mean change from baseline was significantly increased for women taking 4 mg fesoterodine (2.5 days), 8 mg fesoterodine (3 days), and 4 mg tolterodine (2.3 days), compared with placebo (1.7 days). The change in continent days per week was significantly greater for women on 8 mg fesoterodine than for women on 4 mg tolterodine.

A positive treatment response was reported by 49%, 70%, 77%, and 74% in women receiving placebo, 4 mg fesoterodine, 8 mg fesoterodine, and 4 mg tolterodine, respectively. The most common treatment-emergent adverse events at the end of the study were dry mouth, constipation, urinary tract infection, and headache.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg.

SAVANNAH, GA. — Fesoterodine appears to significantly improve the symptoms of overactive bladder in women with an apparent dose-related response, according to a subanalysis of pooled data from two phase III clinical trials involving more than 1,500 women.

Women randomized to either 4 mg or 8 mg of fesoterodine showed significantly greater improvement in the average number of micturitions per day, the average number of urgency urinary incontinence episodes per day, and perceived treatment response, Dr. Peter K. Sand reported in a poster presented at the annual meeting of the Society of Gynecologic Surgeons.

The study was funded by Schwarz BioSciences, a subsidiary of Schwarz Pharma AG, and Pfizer Inc. In 2006, Schwarz Pharma transferred rights for fesoterodine to Pfizer in exchange for an up-front payment of royalties on the combined sales of the drug, if approved. Dr. Sand disclosed that he is an adviser to and an investigator for Pfizer. In addition, another of the study authors is employed by Pfizer.

The researchers pooled data from two phase III randomized controlled trials, which involved male and female patients at least 18 years old with frequency and urgency urinary incontinence. Frequency was defined as at least eight micturitions in 24 hours; urgency urinary incontinence was defined as at least one episode in 24 hours. This subanalysis examined efficacy and tolerability in 1,543 women.

The women were randomized to 12 weeks of treatment with 4 mg fesoterodine (434), 8 mg fesoterodine (452), or placebo (430). One trial also included a positive control arm with 4 mg tolterodine extended release (227). Patients completed 3-day bladder diaries before randomization and at 2, 8, and 12 weeks after initiating treatment.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg fesoterodine in urgency urinary incontinence episodes per day, number of continent days per week, and perceived treatment response, Dr. Sand, a professor of obstetrics and gynecology at Northwestern University, Chicago, and his associates reported at the meeting, which was jointly sponsored by the American College of Surgeons.

The median change in number of micturitions per day from baseline to trial end (the primary end point) was significantly decreased for women on 4 mg fesoterodine (1.8), 8 mg fesoterodine (1.9), and 4 mg tolterodine (1.9), compared with placebo (1.0).

At 12 weeks, the mean decrease from baseline in the number of episodes of urgency urinary incontinence per day was 2.3 for women on 8 mg fesoterodine. Those on 4 mg fesoterodine, 4 mg tolterodine, and placebo had mean decreases from baseline of 1.9 episodes, 1.7 episodes, and 1.1 episodes per day, respectively. The difference was significantly greater for the treatment groups versus the placebo group.

Mean volume voided significantly increased from baseline in women on 4 mg fesoterodine (25.5 mL/void), 8 mg fesoterodine (32.1 mL/void), and 4 mg tolterodine (26.6 mL/void), compared with placebo (9.4 mL/void).

The researchers extrapolated the number of continent days per week from 3-day bladder diaries. The mean change from baseline was significantly increased for women taking 4 mg fesoterodine (2.5 days), 8 mg fesoterodine (3 days), and 4 mg tolterodine (2.3 days), compared with placebo (1.7 days). The change in continent days per week was significantly greater for women on 8 mg fesoterodine than for women on 4 mg tolterodine.

A positive treatment response was reported by 49%, 70%, 77%, and 74% in women receiving placebo, 4 mg fesoterodine, 8 mg fesoterodine, and 4 mg tolterodine, respectively. The most common treatment-emergent adverse events at the end of the study were dry mouth, constipation, urinary tract infection, and headache.

Women on 8 mg fesoterodine showed significantly greater improvement than those on 4 mg.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

SAVANNAH, GA. — Vaginal delivery—but not cesarean section delivery—appears to confer increased risk of stage 2 pelvic organ prolapse, based on the results of a study of almost 300 women.

“Vaginal parity—and not parity alone—was found to be a risk factor for prolapse severity,” wrote Dr. Lieschen Quiroz, of the obstetrics and gynecology department at Johns Hopkins Bayview Medical Center in Baltimore, and her colleagues regarding their study, which was presented as a poster at the annual meeting of the Society of Gynecologic Surgeons, jointly sponsored by the American College of Surgeons.

Each vaginal delivery was associated with a 35% increase in the risk of stage 2 or greater pelvic organ prolapse, while C-sections were not.

The researchers included all women seeking outpatient gynecologic and urogynecologic care at five locations in Baltimore.

Women were excluded if they either were pregnant or were not sexually active. Demographic data and childbirth history were collected.

The women also underwent Pelvic Organ Prolapse Quantitative (POP-Q) examination.

POP-Q data and childbirth history were available for 299 women.

Mean parity increased with increasing prolapse stage—from 1.4 for stage 0 to 3.1 for stage 3.

Age was also statistically associated with increasing prolapse stage.

Race, body mass index, and hysterectomy status were not associated with increasing prolapse stage.

For each vaginal birth, the relative odds ratio for having stage 2–4 prolapse was 1.35; for each C-section birth, the relative odds ratio for having stage 2–4 prolapse was 0.9. The findings suggest that delivery method may be a modifiable risk.

Dr. Quiroz stated that she had no relevant financial relationships to disclose.

CHICAGO — The wakefulness-promoting drug modafinil (marketed as Provigil) reduced self-reported severe fatigue, according to a recent study of more than 600 cancer patients who were undergoing chemotherapy.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Dr. Morrow presented his study's findings at the annual meeting of the American Society of Clinical Oncology.

Study participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle.

They rated fatigue on a 10-point scale: mild (1–4), moderate (5–6), and severe (7–10).

A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant.

This was not surprising, Dr. Morrow commented during a press briefing.

“With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemobrain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemobrain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemobrain.

Cancer-related fatigue appears to particularly affect tasks associated with executive function.

Cancer patients complain of not being able to “get around” to doing things they know they should do.

The pharmaceutical company Cephalon Inc. provided modafinil and placebo for the trial.

Dr. Morrow reported that he has no relevant financial relationships to disclose.

CHICAGO — The wakefulness-promoting drug modafinil (marketed as Provigil) reduced self-reported severe fatigue, according to a recent study of more than 600 cancer patients who were undergoing chemotherapy.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Dr. Morrow presented his study's findings at the annual meeting of the American Society of Clinical Oncology.

Study participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle.

They rated fatigue on a 10-point scale: mild (1–4), moderate (5–6), and severe (7–10).

A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant.

This was not surprising, Dr. Morrow commented during a press briefing.

“With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemobrain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemobrain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemobrain.

Cancer-related fatigue appears to particularly affect tasks associated with executive function.

Cancer patients complain of not being able to “get around” to doing things they know they should do.

The pharmaceutical company Cephalon Inc. provided modafinil and placebo for the trial.

Dr. Morrow reported that he has no relevant financial relationships to disclose.

CHICAGO — The wakefulness-promoting drug modafinil (marketed as Provigil) reduced self-reported severe fatigue, according to a recent study of more than 600 cancer patients who were undergoing chemotherapy.

Gary R. Morrow, Ph.D., of the University of Rochester (N.Y.) and his colleagues randomized 631 patients undergoing four cycles of chemotherapy to receive either 200 mg modafinil daily or placebo. Among those with severe fatigue at baseline, patients on modafinil had significantly greater reductions in fatigue, compared with those on placebo.

Dr. Morrow presented his study's findings at the annual meeting of the American Society of Clinical Oncology.

Study participants were asked to rate their level of fatigue at baseline (during the second cycle of chemotherapy) and during the final cycle.

They rated fatigue on a 10-point scale: mild (1–4), moderate (5–6), and severe (7–10).

A total of 67 patients reported mild fatigue at baseline; 106 and 458 reported moderate and severe fatigue, respectively.

Among patients with mild and moderate fatigue, modafinil also reduced fatigue, compared with placebo, but the differences were not significant.

This was not surprising, Dr. Morrow commented during a press briefing.

“With side effects, quite often the potency of the effect is somewhat dependent on where you began,” he said.

Modafinil—a nonamphetamine stimulant—is currently indicated for the treatment of excessive sleepiness resulting from obstructive sleep apnea, shift-work sleep disorder, and narcolepsy. Last year, researchers also at the University of Rochester reported success with modafinil in treating “chemobrain,” a reduction in cognitive function that has been associated with chemotherapy.

There may be some overlap between chemobrain and fatigue, Dr. Morrow said in an interview. Problems with executive function are commonly described in chemobrain.

Cancer-related fatigue appears to particularly affect tasks associated with executive function.

Cancer patients complain of not being able to “get around” to doing things they know they should do.

The pharmaceutical company Cephalon Inc. provided modafinil and placebo for the trial.

Dr. Morrow reported that he has no relevant financial relationships to disclose.

PHILADELPHIA — E-mail and fax are the preferred tools for pediatric hospitalists to use when communicating with referring physicians, according to the results of a small survey of 77 physicians.

In this survey of referring pediatricians and emergency physicians in the metropolitan Washington area, most preferred follow-up contact from pediatric hospitalists via fax (34%) or e-mail (30%), Dr. Riva Kamat-Nerikar reported at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Kamat-Nerikar, a pediatric hospitalist at Inova Fairfax Hospital for Children in Falls Church, Va., and her colleagues contacted physicians in 38 pediatric practices and 10 emergency departments that referred patients to the pediatric hospitalist service at Inova. The hospitalist team there admits about 2,300 patients per year.

The initial survey contact was Web based. Those who did not respond via the Web were then contacted by fax. Those who did not respond via fax were then contacted by phone.

In all, 77 physicians responded; 74% were pediatric physicians.

Slightly more than half of the respondents were women (56%).

Dr. Kamat-Nerikar noted that almost half of the respondents graduated from medical school after 1990.

Most of the respondents (94%) said that communication from hospitalists was necessary to follow-up care. Ease, accuracy, and directness of the communication from hospitalists were important to the primary care and emergency department physicians, the authors reported.

The most important information in hospitalist communication was the diagnosis, the results of any consults, and laboratory/radiology results, the investigators observed.

PHILADELPHIA — E-mail and fax are the preferred tools for pediatric hospitalists to use when communicating with referring physicians, according to the results of a small survey of 77 physicians.

In this survey of referring pediatricians and emergency physicians in the metropolitan Washington area, most preferred follow-up contact from pediatric hospitalists via fax (34%) or e-mail (30%), Dr. Riva Kamat-Nerikar reported at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Kamat-Nerikar, a pediatric hospitalist at Inova Fairfax Hospital for Children in Falls Church, Va., and her colleagues contacted physicians in 38 pediatric practices and 10 emergency departments that referred patients to the pediatric hospitalist service at Inova. The hospitalist team there admits about 2,300 patients per year.

The initial survey contact was Web based. Those who did not respond via the Web were then contacted by fax. Those who did not respond via fax were then contacted by phone.

In all, 77 physicians responded; 74% were pediatric physicians.

Slightly more than half of the respondents were women (56%).

Dr. Kamat-Nerikar noted that almost half of the respondents graduated from medical school after 1990.

Most of the respondents (94%) said that communication from hospitalists was necessary to follow-up care. Ease, accuracy, and directness of the communication from hospitalists were important to the primary care and emergency department physicians, the authors reported.

The most important information in hospitalist communication was the diagnosis, the results of any consults, and laboratory/radiology results, the investigators observed.

PHILADELPHIA — E-mail and fax are the preferred tools for pediatric hospitalists to use when communicating with referring physicians, according to the results of a small survey of 77 physicians.

In this survey of referring pediatricians and emergency physicians in the metropolitan Washington area, most preferred follow-up contact from pediatric hospitalists via fax (34%) or e-mail (30%), Dr. Riva Kamat-Nerikar reported at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Kamat-Nerikar, a pediatric hospitalist at Inova Fairfax Hospital for Children in Falls Church, Va., and her colleagues contacted physicians in 38 pediatric practices and 10 emergency departments that referred patients to the pediatric hospitalist service at Inova. The hospitalist team there admits about 2,300 patients per year.

The initial survey contact was Web based. Those who did not respond via the Web were then contacted by fax. Those who did not respond via fax were then contacted by phone.

In all, 77 physicians responded; 74% were pediatric physicians.

Slightly more than half of the respondents were women (56%).

Dr. Kamat-Nerikar noted that almost half of the respondents graduated from medical school after 1990.

Most of the respondents (94%) said that communication from hospitalists was necessary to follow-up care. Ease, accuracy, and directness of the communication from hospitalists were important to the primary care and emergency department physicians, the authors reported.

The most important information in hospitalist communication was the diagnosis, the results of any consults, and laboratory/radiology results, the investigators observed.

TAMPA – Methadone is an excellent choice for pain management when the prescribing complexities are understood, said two experts at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

“While it's probably the best opioid analgesic out there, it's also probably the most dangerous,” said Dr. Jane E. Loitman, who is the medical director for the palliative care service at Barnes-Jewish Hospital in St. Louis.

Methadone, a synthetic opioid that is available in the United States as a racemic mixture of two isomers, has several advantages over other opioid analgesics.

“Methadone is the only opioid that acts as an NMDA [N-methyl-D-aspartate] receptor antagonist as well as acting as a mu-[opioid] agonist,” said Dr. Gail Gazelle of Harvard Medical School, Boston. Other opioids work only as mu-opioid agonists. “Methadone also acts as a mu agonist but has this unique property, unlike all of the other opioids, that blocks NMDA receptors.” This action on NMDA receptors makes methadone an excellent choice for the treatment of neuropathic pain. And methadone does not appear to carry the same risk of respiratory depression as other opioids because of NMDA-receptor blockade, Dr. Gazelle said. There is also some evidence that because of the NMDA-receptor antagonism property, methadone has an antitussive action.

In addition, NMDA activity “may mean that it reduces some of the cross-tolerance that we see with patients being converted from another opioid to methadone,” she said. Because NMDA antagonism is one of the mechanisms to prevent tolerance and inhibit neuronal excitation, “methadone may be the drug of choice as an opioid analgesic for someone who has hyperalgesia,” Dr. Loitman said.

Methadone typically has very little euphoric effect, which can be advantageous when there is a concern about diversion. Methadone has no known active metabolites and blocks serotonin/norepinephrine uptake. Another “important advantage of methadone is that it is the only opioid that is fecally excreted. So it's an excellent medication to use for patients with known chronic renal insufficiency,” she said.

Methadone also has fewer of the neuroexcitatory side effects of opioids, such as myoclonus and delirium, and may be associated with a lower incidence of constipation than other opioids. The drug can be given orally, rectally, sublingually, intravenously, subcutaneously, and transdermally. It has a very high potency when used after another opioid, and its oral bioavailability is very high (85%), compared with roughly 35% for morphine.

“If you have a DEA license to prescribe other schedule II medications, you can prescribe methadone,” Dr. Loitman said. No special license is required, and one doesn't need to be a pain specialist to prescribe this drug. But “before you start someone on methadone, you need to understand the pharmacology, the side effects, the advantages and disadvantages, the myths, and who you're prescribing it for,” she said.

Despite methadone's attractiveness for the treatment of pain, it's a complicated drug to prescribe. Methadone is difficult to dose and equianalgesia is a particular problem, because the analgesic and biologic half-lives don't match. While the biologic half-life of methadone can range from 18 to almost 100 hours (average, about 24 hours), the analgesic half-life ranges from 6 to 12 hours. “So the steady state of methadone–because of its long half-life–can take a while to reach,” Dr. Gazelle said. Reaching a steady state takes about five biologic half-lives, she said.

Methadone also has a risk of cumulative toxicity because of its long and unpredictable biologic half-life, and it's necessary to titrate this drug more slowly than other opioids. Because methadone is lipophilic, it can be difficult to titrate the drug in elderly patients, who have a greater percentage of adipose tissue.

Another complication is that methadone is metabolized through the cytochrome P450 system, which is induced by a number of other drugs, including phenytoin and rifampin. Larger doses of methadone might be needed when a patient is also on one of these drugs. “It's almost impossible to get therapeutic levels of methadone in patients on rifampin,” Dr. Gazelle said. Other medications, including azole antifungal agents and macrolide antibiotics, might inhibit the cytochrome P450 system and require decreased doses of methadone. Therefore, it is important to review all of the drugs that a patient is on before prescribing methadone.

In 2006, the Food and Drug Administration issued a public health advisory for methadone, in part because of reports of QTc interval prolongation and serious arrhythmia (torsades de pointes) that had been observed during treatment with methadone. Most of these cases involved patients in pain who were receiving large, multiple daily doses.

“I don't think there is any standard of care that has developed. I think that we probably need to be cognizant of the fact that methadone may prolong the QTc interval,” Dr. Gazelle said. She advises thinking about what the goals of care are for individual patients and discussing with them the potential cardiac risks.

There are several opioid/methadone conversion protocols, including the U.K. Hospice model (Pain Rev. 1998;5:51-8), the Milan model (J. Clin. Oncol. 1998;16:3216-21), the Edmonton model (Cancer 1996;78:852-7), the German model (Am. J. Hosp. Palliat. Care 2001;18:200-2), and the Royal Perth Hospital model (Med. J. Aust. 2000;173:536-40).

For physicians with adequate experience prescribing methadone, the drug should be considered under the following circumstances:

▸ When starting a patient on a long-acting opioid.

▸ For patients already on very high doses of a long-acting opioid.

▸ When side effects from current pain medications are unacceptable.

▸ When a patient has inadequate pain control.

▸ For the treatment of neuropathic pain.

▸ For patients with current or recurrent substance abuse problems.

▸ When there is concern about drug diversion.

Despite the complexity of proper use, with methadone “we can really change a patient's level of suffering, in ways that we sometimes can't with other opioids,” Dr. Gazelle observed.

Neither Dr. Loitman nor Dr. Gazelle had any relevant financial relationships to disclose.

TAMPA – Methadone is an excellent choice for pain management when the prescribing complexities are understood, said two experts at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

“While it's probably the best opioid analgesic out there, it's also probably the most dangerous,” said Dr. Jane E. Loitman, who is the medical director for the palliative care service at Barnes-Jewish Hospital in St. Louis.

Methadone, a synthetic opioid that is available in the United States as a racemic mixture of two isomers, has several advantages over other opioid analgesics.

“Methadone is the only opioid that acts as an NMDA [N-methyl-D-aspartate] receptor antagonist as well as acting as a mu-[opioid] agonist,” said Dr. Gail Gazelle of Harvard Medical School, Boston. Other opioids work only as mu-opioid agonists. “Methadone also acts as a mu agonist but has this unique property, unlike all of the other opioids, that blocks NMDA receptors.” This action on NMDA receptors makes methadone an excellent choice for the treatment of neuropathic pain. And methadone does not appear to carry the same risk of respiratory depression as other opioids because of NMDA-receptor blockade, Dr. Gazelle said. There is also some evidence that because of the NMDA-receptor antagonism property, methadone has an antitussive action.

In addition, NMDA activity “may mean that it reduces some of the cross-tolerance that we see with patients being converted from another opioid to methadone,” she said. Because NMDA antagonism is one of the mechanisms to prevent tolerance and inhibit neuronal excitation, “methadone may be the drug of choice as an opioid analgesic for someone who has hyperalgesia,” Dr. Loitman said.

Methadone typically has very little euphoric effect, which can be advantageous when there is a concern about diversion. Methadone has no known active metabolites and blocks serotonin/norepinephrine uptake. Another “important advantage of methadone is that it is the only opioid that is fecally excreted. So it's an excellent medication to use for patients with known chronic renal insufficiency,” she said.

Methadone also has fewer of the neuroexcitatory side effects of opioids, such as myoclonus and delirium, and may be associated with a lower incidence of constipation than other opioids. The drug can be given orally, rectally, sublingually, intravenously, subcutaneously, and transdermally. It has a very high potency when used after another opioid, and its oral bioavailability is very high (85%), compared with roughly 35% for morphine.

“If you have a DEA license to prescribe other schedule II medications, you can prescribe methadone,” Dr. Loitman said. No special license is required, and one doesn't need to be a pain specialist to prescribe this drug. But “before you start someone on methadone, you need to understand the pharmacology, the side effects, the advantages and disadvantages, the myths, and who you're prescribing it for,” she said.

Despite methadone's attractiveness for the treatment of pain, it's a complicated drug to prescribe. Methadone is difficult to dose and equianalgesia is a particular problem, because the analgesic and biologic half-lives don't match. While the biologic half-life of methadone can range from 18 to almost 100 hours (average, about 24 hours), the analgesic half-life ranges from 6 to 12 hours. “So the steady state of methadone–because of its long half-life–can take a while to reach,” Dr. Gazelle said. Reaching a steady state takes about five biologic half-lives, she said.

Methadone also has a risk of cumulative toxicity because of its long and unpredictable biologic half-life, and it's necessary to titrate this drug more slowly than other opioids. Because methadone is lipophilic, it can be difficult to titrate the drug in elderly patients, who have a greater percentage of adipose tissue.

Another complication is that methadone is metabolized through the cytochrome P450 system, which is induced by a number of other drugs, including phenytoin and rifampin. Larger doses of methadone might be needed when a patient is also on one of these drugs. “It's almost impossible to get therapeutic levels of methadone in patients on rifampin,” Dr. Gazelle said. Other medications, including azole antifungal agents and macrolide antibiotics, might inhibit the cytochrome P450 system and require decreased doses of methadone. Therefore, it is important to review all of the drugs that a patient is on before prescribing methadone.

In 2006, the Food and Drug Administration issued a public health advisory for methadone, in part because of reports of QTc interval prolongation and serious arrhythmia (torsades de pointes) that had been observed during treatment with methadone. Most of these cases involved patients in pain who were receiving large, multiple daily doses.

“I don't think there is any standard of care that has developed. I think that we probably need to be cognizant of the fact that methadone may prolong the QTc interval,” Dr. Gazelle said. She advises thinking about what the goals of care are for individual patients and discussing with them the potential cardiac risks.

There are several opioid/methadone conversion protocols, including the U.K. Hospice model (Pain Rev. 1998;5:51-8), the Milan model (J. Clin. Oncol. 1998;16:3216-21), the Edmonton model (Cancer 1996;78:852-7), the German model (Am. J. Hosp. Palliat. Care 2001;18:200-2), and the Royal Perth Hospital model (Med. J. Aust. 2000;173:536-40).

For physicians with adequate experience prescribing methadone, the drug should be considered under the following circumstances:

▸ When starting a patient on a long-acting opioid.

▸ For patients already on very high doses of a long-acting opioid.

▸ When side effects from current pain medications are unacceptable.

▸ When a patient has inadequate pain control.

▸ For the treatment of neuropathic pain.

▸ For patients with current or recurrent substance abuse problems.

▸ When there is concern about drug diversion.

Despite the complexity of proper use, with methadone “we can really change a patient's level of suffering, in ways that we sometimes can't with other opioids,” Dr. Gazelle observed.

Neither Dr. Loitman nor Dr. Gazelle had any relevant financial relationships to disclose.

TAMPA – Methadone is an excellent choice for pain management when the prescribing complexities are understood, said two experts at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association.

“While it's probably the best opioid analgesic out there, it's also probably the most dangerous,” said Dr. Jane E. Loitman, who is the medical director for the palliative care service at Barnes-Jewish Hospital in St. Louis.

Methadone, a synthetic opioid that is available in the United States as a racemic mixture of two isomers, has several advantages over other opioid analgesics.

“Methadone is the only opioid that acts as an NMDA [N-methyl-D-aspartate] receptor antagonist as well as acting as a mu-[opioid] agonist,” said Dr. Gail Gazelle of Harvard Medical School, Boston. Other opioids work only as mu-opioid agonists. “Methadone also acts as a mu agonist but has this unique property, unlike all of the other opioids, that blocks NMDA receptors.” This action on NMDA receptors makes methadone an excellent choice for the treatment of neuropathic pain. And methadone does not appear to carry the same risk of respiratory depression as other opioids because of NMDA-receptor blockade, Dr. Gazelle said. There is also some evidence that because of the NMDA-receptor antagonism property, methadone has an antitussive action.

In addition, NMDA activity “may mean that it reduces some of the cross-tolerance that we see with patients being converted from another opioid to methadone,” she said. Because NMDA antagonism is one of the mechanisms to prevent tolerance and inhibit neuronal excitation, “methadone may be the drug of choice as an opioid analgesic for someone who has hyperalgesia,” Dr. Loitman said.

Methadone typically has very little euphoric effect, which can be advantageous when there is a concern about diversion. Methadone has no known active metabolites and blocks serotonin/norepinephrine uptake. Another “important advantage of methadone is that it is the only opioid that is fecally excreted. So it's an excellent medication to use for patients with known chronic renal insufficiency,” she said.

Methadone also has fewer of the neuroexcitatory side effects of opioids, such as myoclonus and delirium, and may be associated with a lower incidence of constipation than other opioids. The drug can be given orally, rectally, sublingually, intravenously, subcutaneously, and transdermally. It has a very high potency when used after another opioid, and its oral bioavailability is very high (85%), compared with roughly 35% for morphine.

“If you have a DEA license to prescribe other schedule II medications, you can prescribe methadone,” Dr. Loitman said. No special license is required, and one doesn't need to be a pain specialist to prescribe this drug. But “before you start someone on methadone, you need to understand the pharmacology, the side effects, the advantages and disadvantages, the myths, and who you're prescribing it for,” she said.

Despite methadone's attractiveness for the treatment of pain, it's a complicated drug to prescribe. Methadone is difficult to dose and equianalgesia is a particular problem, because the analgesic and biologic half-lives don't match. While the biologic half-life of methadone can range from 18 to almost 100 hours (average, about 24 hours), the analgesic half-life ranges from 6 to 12 hours. “So the steady state of methadone–because of its long half-life–can take a while to reach,” Dr. Gazelle said. Reaching a steady state takes about five biologic half-lives, she said.

Methadone also has a risk of cumulative toxicity because of its long and unpredictable biologic half-life, and it's necessary to titrate this drug more slowly than other opioids. Because methadone is lipophilic, it can be difficult to titrate the drug in elderly patients, who have a greater percentage of adipose tissue.

Another complication is that methadone is metabolized through the cytochrome P450 system, which is induced by a number of other drugs, including phenytoin and rifampin. Larger doses of methadone might be needed when a patient is also on one of these drugs. “It's almost impossible to get therapeutic levels of methadone in patients on rifampin,” Dr. Gazelle said. Other medications, including azole antifungal agents and macrolide antibiotics, might inhibit the cytochrome P450 system and require decreased doses of methadone. Therefore, it is important to review all of the drugs that a patient is on before prescribing methadone.

In 2006, the Food and Drug Administration issued a public health advisory for methadone, in part because of reports of QTc interval prolongation and serious arrhythmia (torsades de pointes) that had been observed during treatment with methadone. Most of these cases involved patients in pain who were receiving large, multiple daily doses.

“I don't think there is any standard of care that has developed. I think that we probably need to be cognizant of the fact that methadone may prolong the QTc interval,” Dr. Gazelle said. She advises thinking about what the goals of care are for individual patients and discussing with them the potential cardiac risks.

There are several opioid/methadone conversion protocols, including the U.K. Hospice model (Pain Rev. 1998;5:51-8), the Milan model (J. Clin. Oncol. 1998;16:3216-21), the Edmonton model (Cancer 1996;78:852-7), the German model (Am. J. Hosp. Palliat. Care 2001;18:200-2), and the Royal Perth Hospital model (Med. J. Aust. 2000;173:536-40).

For physicians with adequate experience prescribing methadone, the drug should be considered under the following circumstances:

▸ When starting a patient on a long-acting opioid.

▸ For patients already on very high doses of a long-acting opioid.

▸ When side effects from current pain medications are unacceptable.

▸ When a patient has inadequate pain control.

▸ For the treatment of neuropathic pain.

▸ For patients with current or recurrent substance abuse problems.

▸ When there is concern about drug diversion.

Despite the complexity of proper use, with methadone “we can really change a patient's level of suffering, in ways that we sometimes can't with other opioids,” Dr. Gazelle observed.

Neither Dr. Loitman nor Dr. Gazelle had any relevant financial relationships to disclose.